Buffer

Overview

Buffered Solutions
• Definition
• Buffer equation
• Buffer capacity
• Buffer in biological systems
• Pharmaceutical buffers

Isotonic solutions
• Introduction
• Isotonic solution
• Method of adjusting tonicity
Buffers

Buffers are mixtures of Buffer is composed of a

compounds that resist weak acid (HA) and its
changes in pH when small salt (conjugate base A-) or
amounts of acid or alkali a weak base and its salt
is added to them. (conjugate acid HB+).
 pH

When an acid or a base is

added to water, the pH
changes drastically.
In a buffer solution, the
pH is maintained; pH does
not change when acids or
bases are added.
 Function of a weak acid in an
acidic buffer
If a small amount of base is added to the buffer solution, it is
neutralized by the acetic acid, CH3COOH, which shifts the
equilibrium in the direction of the products acetate ion and
water.

CH3COOH + OH− → CH3COO− + H2O

so, the pH will not change significantly
 Function of Conjugate Base in an
acidic Buffer
When a small amount of acid is added, it will be buffered by another
reaction, this time using the salt (CH3COO-)
The acetic acid produced contributes to the available weak acid.
CH3COONa + H+ → CH3COO- + Na+
The pH will not alter significantly because the CH3COOH formed is a weak
acid
Function of basic buffer
• Weak base such as ammonium (NH4OH) and its salt
(NH4Cl)

• On addition of strong acid:

H+ + NH4OH → NH4+ + H2O

• On addition of strong base:

OH- + NH4+ → NH4OH
 Buffer Equation
The previous equation is known as the buffer equation or the
Henderson–Hasselbalch equation.
For a weak acid (𝑯𝑨) and its salt (𝑺):
[𝑺]
𝒑 𝑯 = 𝒑𝑲𝒂 +𝒍𝒐𝒈
[HA]
For a weak Base (𝑩) and its salt (𝑺):
[B]
𝒑 𝑯 = 𝒑𝑲𝒂 +𝒍𝒐𝒈
[𝑺]
Buffer solutions are not commonly prepared from weak bases and
their salts because of:
1. Volatility and instability of the bases
2. Dependence of their 𝒑𝑯 on 𝒑𝑲𝒘 , which is often affected by
temperature changes.
• pKa= -log Ka

• Ka is the dissociation constant of the acid

• [A-] is the concentration of the base

• [HA] is the concentration of the acid

• 𝒑𝑲 𝒂 = 𝒑 𝑲 𝒘 − 𝒑𝑲 𝒃

• pk w = - log of water (Kw) = 14

• pK b = - log of dissociation constant of base
(Kb)
 Buffer Equation
Example 1
What is the pH of a buffer solution containing 0.1 M acetic acid
and 0.1 M sodium acetate? (Ka for acetic acid = 1.75 ×10−5)

𝒑𝑲 𝒂 = − 𝒍𝒐𝒈𝑲 𝒂
𝒑𝑲 𝒂 = − l o g 1 . 7 5 ×1 0 −5= 4 . 7 6
[𝑺]
𝒑𝑯 = 𝒑𝑲𝒂 +𝒍𝒐𝒈
[H𝑨]
[0.1]
𝒑𝑯 = 4.76 + 𝑙𝑜𝑔 =4.76
[0.1]
 Buffer Equation
Example 2
How much sodium acetate (mol) should be added to 200 mL of
0.1 mol/L acetic acid solution to prepare a buffer of pH 5.2?
pKa for acetic acid = 4.76

𝒑𝑯 = 𝒑𝑲𝒂 +𝒍𝒐𝒈 [𝑺]

[H𝑨]
[𝑺]
𝟓.𝟐 =𝟒 .𝟕𝟔+𝒍𝒐𝒈
[𝟎.𝟏]

𝑺 = 0.2754mol/L

𝒏 sodium acetate = 𝑴 ×𝒗 = 0. 2 754 ×0.2= 0.055 mol

 Buffer Equation
Example 3
What is the pH of a solution containing ephedrine 0.1 M and
ephedrine HCl 0.01 M? (Kb for ephedrine = 2.3 × 10-5)

𝒑𝑲 𝒃 = − 𝒍𝒐𝒈𝑲 𝒃
𝒑𝑲 𝒃 = − l o g 2. 3 ×1 0 −5=4 . 6 4
𝒑𝑲 𝒂 = 𝒑 𝑲 𝒘 − 𝒑𝑲 𝒃
𝒑𝑲 𝒂 = 1 4 − 4 . 6 4 = 9. 3 6

[𝑩 ]
𝒑𝑯 = 𝒑𝑲𝒂+ 𝒍𝒐𝒈
[𝑺]
0.1
𝒑𝑯 = 9.36 + 𝑙𝑜𝑔 =10.36
0.01
 Buffer Capacity
Definition

Buffer capacity is the quantity

of strong acid or base that must
be added to change the pH of
one liter of buffer solution by
one pH unit.
 Buffer Capacity
Approximate Equation
Koppel and Spiro and Van Slyke devised an approximate
equation for calculating buffer capacity (𝜷):

𝜷 = 𝜟𝑩
𝜟𝒑𝑯
𝜟𝑩: number of moles of strong acid or base per liter of buffer.
𝜟𝒑𝑯: change in pH.
When one of the buffer components is depleted completely,
the solution lose its buffering capacity and can no longer
resist the change in pH
 Buffer Capacity
Exact Equation
Koppel and Spiro and Van Slyke developed a more exact
Equation for calculating buffer capacity:
𝑲 [𝑯 𝑶 +]
𝒂 𝟑
𝜷 = 𝟐.𝟑𝑪 𝟐
(𝑲 𝒂 + 𝑯 𝟑𝑶 +
𝑪 is the total buffer concentration (the sum of the molar concentrations of
the acid and the salt).
This equation allows the calculation of buffer capacity at any
pH (even when no acid or base has been added to the
buffer).
The equation shows that an increase in the concentration of
the buffer components ( 𝑪 ) results in a greater buffer
capacity (𝜷).
 Buffer Capacity
Exact Equation
Example
At a hydrogen ion concentration of 1.75 × 10–5, what is the
capacity of a buffer containing 0.10 mole each of acetic acid
and sodium acetate per liter of solution? (Ka = 1.75 × 10–5 )
C = [Acid] + [Salt] = 0.1+ 0.1 = 0.20 mole/liter

𝑲 𝒂 [𝑯 𝟑 𝑶 + ]
𝜷 = 𝟐.𝟑𝑪
(𝑲 𝒂 + [𝑯 𝟑𝑶 +] 𝟐

(1.75 × 10–5)(1.75 × 10–5)

𝜷 = 𝟐 . 𝟑× 0.2× = 0.115𝑚𝑜𝑙/𝐿
(1.75 × 10–5) + (1.75 × 10–5)2
 Buffer Capacity

Maximum Buffer Capacity

The buffer capacity depends on:
(a) the value of the ratio [Salt]/[Acid], (buffer capacity increases
as the ratio approaches 1)

(b) The total buffer concentration (buffer capacity increases

as the salt and acid concentrations are increased).
 Buffer Capacity

Maximum Buffer Capacity

The maximum buffer capacity occurs where pH = pKa, or, in
equivalent terms, where pH = pKa (or [H3O+] = Ka).

𝜷 𝒎 𝒂 𝒙 = 𝟎. 𝟓𝟕𝟔𝑪
Where C is the total buffer concentration
 Buffer Capacity
Maximum Buffer Capacity
Example
What is the maximum buffer capacity of an acetate buffer with
a total concentration of 0.020 mole/liter?
𝜷 𝒎 𝒂 𝒙 = 𝟎. 𝟓𝟕𝟔𝑪
𝜷 𝒎 𝒂 𝒙 = 0.576 ×0.02 = 0.012
 Buffer in Biological Systems
Some body fluids have natural buffer capacity:
1. pH of tears is 7-8 with higher buffer capacity so that a
reasonably wide pH range of medicines can be tolerated.
2. pH of blood is maintained at approximately 7.4 by buffer
component in the plasma (bicarbonate and phosphate
buffers) and erythrocytes (hemoglobin and phosphate
buffers).
H2CO3 ↔ HCO3− + H+
H2PO4 ↔ HPO42− + H+

HbH+ + O2 ↔ + O2Hb + H+
Hb: hemoglobin, O2Hb: oxyhemoglobin
 Pharmaceutical Buffers
Buffer solutions are widely used to adjust pH of aqueous
pharmaceutical solutions to ensure:
1. Tissue irritation prevention
2. Optimum therapeutic effect
3. Maximum drug stability
4. Maximum drug solubility
 Tonicity
• Osmosis is the diffusion of solvent through a semi-
permeable membrane.
• Water always flows from lower solute concentration
[dilute solution] to higher solute concentration until a
balance is produced
• Osmotic pressure is the force that cause this diffusion .
• Tonicity is a measure of the
osmotic pressure of two solutions
separated by a semi-permeable
membrane.
 Isotonic solution
Isotonic solution: a solution having the same
osmotic pressure as a specific body fluid
Hypotonic solution: a solution of lower osmotic
pressure than that of body fluids.
Hypertonic solution: a solution of higher
osmotic pressure than that of body fluids.

Hypotonic isotonic Hypertonic

NaCl 0.2% NaCl 0.9% NaCl 2%

solute
Inside
›outside
solute solute
Inside
=outside
solute solute
Inside
‹outside
solute

swelling equilibrium shrinkage

Methods of Adjusting Tonicity

• Class 1 method: Sodium chloride concentration

added to the drug to make an isotonic solution is
calculated
(1) Cryoscopic method
(2) Sodium chloride equivalent method
• Class 2 method: Amount of water added to the
drug to make an isotonic solution is calculated
(1) White-Vincent Method
(2) Sprowls Method
 Methods of Adjusting Tonicity
Class I Method: Cryoscopic Method
In the cryoscopic method, sodium chloride or some other
substance is added to the solution of the drug to lower the
freezing point depression of the solution to 0.52°C and thus
make it isotonic with body fluids.
 Methods of Adjusting Tonicity
Class I Method: Cryoscopic Method
Example
1% NaCL solution has a freezing pint depression of 0.576.
Isotonic solution of NaCL can be obtained by calculating the
percentage concentration of sodium chloride required to
produce freezing point depression of 0.52 (fpd of blood and
tears) by simple proportion as
1% 0.576 °𝑪
X% 0.52 °𝑪
𝟏% 𝟎.𝟓2°𝑪
= ⟹𝑿 = 𝟎.9 %
𝑿 𝟎.576°𝑪
 Methods of Adjusting Tonicity

Class I Method: NaCl Equivalent Method

The sodium chloride equivalent (E) of a drug is the amount of
sodium chloride that has the same osmotic effect of 1 g of
the drug.

In the NaCl equivalent method, sodium chloride or some other

substance is added to the solution of the drug to make the
concentration of the solution equivalent to 0.9% of NaCl and
thus make it isotonic with body fluids.
 Methods of Adjusting Tonicity
Class I Method: NaCl Equivalent Method
Example 2
A solution contains 1.0 g of ephedrine sulfate in a volume of
100 mL. What quantity of sodium chloride must be added to
make the solution isotonic? E value for the drug is 0.23
The quantity of the drug is multiplied by its NaCl equivalent, E :
Ephedrine sulfate: 1 g × 0.23 = 0.23 g
The ephedrine sulfate has contributed a weight of material
osmotically equivalent to 0.23 g of NaCl.
Because a total of 0.9 g of NaCl is required for isotonicity, 0.67
g (0.90 - 0.23 g) of NaCl must be added.
 Methods of Adjusting Tonicity
Class II Method: White-Vincent Method
The class II methods of computing tonicity involve the addition
of water to the drugs to make an isotonic solution, followed
by the addition of an isotonic-buffered diluting vehicle to
bring the solution to the final volume.
White and Vincent developed a simplified equation for
calculating the volume V (mLs) of isotonic solution prepared
by mixing the drug with water.
𝑽 =𝒘 ×𝑬 ×𝟏𝟏𝟏.𝟏
w : weight (g) of the drug.
E : NaCl equivalent
 Methods of Adjusting Tonicity
Class II Method: White-Vincent Method
Example 1
How to make 30 mL of a 1% solution of procaine HCl isotonic
with body fluid? NaCl equivalent for procaine HCl is 0.21
Weight of the drug = 30 × 1% = 0.3 g
𝑽 =𝒘 ×𝑬 ×𝟏𝟏𝟏.𝟏
𝑽 = 0.3 ×0.21 ×111.1 = 7 ml
7 ml of water is added to the drug to make it isotonic, then
enough isotonic diluting solution is added to make 30 mL of
the finished product.
 Methods of Adjusting Tonicity
Class II Method: White-Vincent Method
Example 2
Make the following solution isotonic with body fluid:
Phenacaine HCl………………………….0.06 g
Boric acid…………………………………0.30 g
DW, enough to make…………………100 ml
E for Phenacaine HCl and Boric acid are 0.2 and 0.5 respectively
𝑽PhenacaineHCL= 0.06 ×0.20 ×111.1 = 1.33 ml
𝑽Boric acid= 0.3 ×0.5 ×111.1 = 16.66 ml
𝑽Total = 1.33 + 16.66 = 18 ml
The drugs are mixed with water to make 18 mL of an isotonic
solution, and the volume of the preparation is completed to
100 mL by adding an isotonic diluting solution.
 Methods of Adjusting Tonicity
Class II Method: Sprowls Method
Sprowls method is a simplification of White-Vincent Method in
which V values for drugs of fixed weights (0.3 g) are
computed and constructed as a table.